Variant chr5-75104811-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001372053.1(ANKRD31):c.4748G>A(p.Cys1583Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,537,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ANKRD31
NM_001372053.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.878

Variant links:

Genes affected

ANKRD31 (HGNC:26853): (ankyrin repeat domain 31) This gene encodes a protein containing multiple ankyrin repeats. Ankyrin domains function in protein-protein interactions in a variety of cellular processes. Mutations in this gene are associated with a Rett syndrome (RTT)-like phenotype. [provided by RefSeq, Apr 2017]

ANKRD31 links:

ANKRD31 (HGNC:):

ANKRD31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01044932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD31	NM_001372053.1 linkuse as main transcript	c.4748G>A	p.Cys1583Tyr	missense_variant	22/26	ENST00000506364.6	NP_001358982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD31	ENST00000506364.6 linkuse as main transcript	c.4748G>A	p.Cys1583Tyr	missense_variant	22/26	5	NM_001372053.1	ENSP00000427262.2		D6RJB7

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000282

AC:

AN:

141742

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

75796

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.000285

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000143

AC:

198

AN:

1384902

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

683372

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000286

Gnomad4 NFE exome

AF:

0.0000983

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.000584

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000398

Hom.:

Bravo

AF:

0.000744

ESP6500AA

AF:

0.00217

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2023

The c.4577G>A (p.C1526Y) alteration is located in exon 21 (coding exon 21) of the ANKRD31 gene. This alteration results from a G to A substitution at nucleotide position 4577, causing the cysteine (C) at amino acid position 1526 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

ANKRD31-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.26

DANN

Benign

0.64

DEOGEN2

Benign

0.0091

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.071

Sift

Benign

0.11

.;T

Sift4G

Benign

0.10

T;T

Vest4

0.11

MVP

0.12

ClinPred

0.011

GERP RS

-6.7

Varity_R

0.085

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over